KR900006555B1 - 1,2,4-oxadiazole derivatives and preparation method thereof - Google Patents

Abstract

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Description

Oxadiazol derivatives and preparation method thereof

The present invention relates to 1,2,4-oxadiazole derivatives of the general formula (I) below which are useful as herbicides and methods for their preparation.

Wherein R ¹ is dichlorophenoxymethyl, benzyl, ethyl, amido, lower alkylaminocarbonyl, methoxycarbonylamino, lower alkylureido, ethoxycarbonylalkoxy, diethylthiocarbamoylmethylyl , Allylaminocarbonyl substituted with one or two halogens, phenyl, R ² is dichlorophenoxymethyl, hydroxy, chloro, diethylthiocarbamoylmethyl, ethoxycarbonylalkoxyalkoxyoxy , Ethoxycarbonylalkoxyphenoxy, dichlorophenoxy, nitrophenoxy, ethoxycarbonyl, amido, lower alkylaminocarbonyl and diethylphosphonyl.

Since 1,600, 1,2,4-oxadiazole-based compounds have been used in medicines such as anesthetics, analgesic crabs, anti-inflammatory drugs, etc., since 1960, as well as the development of various synthetic methods and studies on physiological activity. Besides, it is also used as a surface treatment agent for fibers, intermediates for dyes, and polymer additives.

Recently, organic compounds containing heterocycles such as thiazole, thiadiazole, isoxazazole, and pyrazole are used as pesticides, and 1,2,4-oxadiazole-based compounds are used as fungicides, nematicides, herbicides, etc. Is being developed. In particular, the compounds known to be effective as herbicides are those in which 1,2,4-oxadiazole structures are substituted in the side chains of compounds such as amides, diphenyl ethers, and sulfonylureas, which are known as herbicide structures. 3,822,280, JP 2,801,509, 2,842,248, 3,122,340, US 4,166,732, 161,882, 192,706, 111,442, JP 61-63,668, etc. Disclosed in the specification. As described above, 1,2,4-oxadiazole-based compounds are greatly expected as herbicides, and are still being researched and developed in the art.

To be an ideal herbicide, not only should we have selective weed control with a small amount of l use throughout the entire growing season of weeds, but it must also be non-toxic, essentially harmless to the crops to which the herbicide is applied, and not to contaminate the soil. It must itself decompose or dissipate. Conventional herbicides have been somewhat problematic to recognize as ideal herbicides as described above.

The present inventors have conducted extensive research to solve the above-mentioned shortcomings. As a result, new compounds of 1,2,4-oxadiazole series exhibit strong herbicidal activity against weeds and have a high selectivity between crops and weeds. Discovered and completed the present invention. That is, the compounds of general formula (I) have good or superior herbicidal effect at concentrations of 250 g // ha or less for annual weeds growing in paddy soils, and excellent concentrations of 500 g / ha for perennial weeds that are difficult to control. Herbicidal effect. On the other hand, it is very safe for rice. In addition, it has excellent control effect against broadleaf weeds growing in the field soil and is highly selective because it is safe to corn and wheat with flower.

It is a first object of the present invention to provide 1,2,4-oxadiazole derivatives of the general formula (I).

A second object of the present invention is to provide a method for preparing the 1,2,4-oxadiazole derivatives of the general formula (I).

It is a third object of the present invention to provide a use as a herbicide, characterized in that it contains at least one selected from l, 2,4-oxadiazole derivatives of the above formula (I) as an active ingredient.

Hereinafter, the present invention will be described in detail.

Formula (I) compounds of the present invention can be prepared according to the following methods. However, it is obvious that the present invention is not limited to these methods.

(First method)

[Step 1]

트336"이라 칭함), 18-크라운-6-에테르, 벤질트리에틸암모늄클로라이드와 같은 4급 암모늄염이 바람직하다. 또한 이 반응에 소량의 물을 사용하는 것이 좋으며, 사용량은 용매에 대해 0.1-0.2%(부피)가 바람직하다. 반응온도는 용매의 비등점으로서 30-50℃의 온도가 적당하다.A nitrile of formula (IV) is prepared by reacting a halide of formula (II) with a cyanide of formula (III) in the presence of a solvent and a catalyst. In this reaction, acyl chloride, alkylchloroformate, and the like are used. Is suitable for halogenated hydrocarbons, ethers, etc., and the catalyst is a tricaprylmethylammonium chloride (hereinafter referred to as "allite) as a phase transfer catalyst.

Quaternary ammonium salts, such as 336 "), 18-crown-6-ether and benzyltriethylammonium chloride, are also preferred. A small amount of water is preferred for this reaction and the amount used is 0.1-0.2 for the solvent. % (Volume) is preferred The reaction temperature is preferably 30-50 ° C. as the boiling point of the solvent.

[2 steps]

The nitrile of formula (IV) obtained in step 1 is reacted with hydrogen sulfide of formula (V) at room temperature to 60 캜 in a solvent to obtain a thiocarbamoyl derivative of formula (VI). At this time, hydrogen sulfide is preferably dried and used. As the solvent, benzene, toluene, ether, petroleum ether, hexane and the like are suitable, and the reaction temperature is preferably in the range of room temperature to 60 ° C. It is more preferable to use a base such as diethylamine or triethylamine as the catalyst.

[3 step]

The amide oxime of the general formula (VIII) is prepared by reacting the general formula (VI) obtained in step 2 with the presence of a base and a catalyst. Examples of the base include sodium methoxide, sodium ethoxide, potassium carbonate and sodium carbonate, and examples of the solvent include lower alkyl alcohols.

[4 steps]

The amide oxime of formula (VIII) and the acyl chloride of formula (IX) prepared in step 3 were dried with acetone, acetonitrile, toluene, ethyl acetate, halogenated hydrocarbon, dioxane, ether in the presence of organic or inorganic base. Reaction in a selected solvent such as to prepare a 0-acylamide oxime of formula (X). Examples of the organic base include triethylamine, pyridine, and the like, and examples of the inorganic base include sodium carbonate and potassium monocarbonate.

The reaction temperature is preferably from room temperature to 60 ℃ when using an organic base, the temperature of the boiling point of the solvent is preferred when using an inorganic base.

[5 steps]

The 1,2-4-oxadiazole derivatives of the general formula (Ia) are prepared by subjecting the 0-acylamide oxime of the general formula (X) obtained in step 4 to ring closure in an organic solvent in the presence of a catalyst. At this time, as the catalyst, sodium methoxide, diethylamine, triethylamine, trifluoroboron ether (BF ₃ · Et ₂ O) and the like can be used, and acetone, alcohol, dioxane, toluene and the like are preferable. . The reaction temperature is suitable for the boiling point of the solvent used, the reaction time is preferably 4 to 12 hours.

The method is represented by the reaction scheme as follows.

Wherein R ¹ is as defined above and M represents sodium, potassium or copper.

(Second method)

[Step 1]

The amide oxime of general formula (VIII) is obtained by reacting nitrile of general formula (IV) with a hydrochloride or sulfate salt of hydroxylamine of general formula (VII) or free hydroxylamine obtained by neutralizing it with alkali. At this time, as a solvent used, alcohol, water, etc. are preferable, You may use these individually or in combination of 2 or more types. The reaction temperature is preferably from room temperature to 100 ° C.

[2 steps]

By reacting the amide oxime of general formula (VIII) with the acyl chloride of general formula (XI) to prepare 0-acylamide oxime of general formula (XII), and ring-closing it, l, 2,4 of general formula (XIII) Obtain an oxadiazole derivative. At this time, the reaction conditions are the same as the conditions of step 4-5 of the first method. It is preferable to use trifluoroboron ether (BF ₃ · Et ₂ O) as a catalyst in the ring closure reaction.

[3 step]

Another l, 2,4- of formula (Ib) was reacted by reacting " l, 2,4-oxadiazole of formula (XIII) with acetone solvent dried in the presence of an inorganic base with phenol of formula (XIV). An oxadiazole derivative is obtained, in which the inorganic bases include potassium carbonate and sodium carbonate, and the reaction temperature is preferably the temperature of the boiling point of the solvent.

The above method is represented by the following reaction scheme.

Wherein R ¹ is as defined above and R represents phenyl with a substituent.

(Third method)

[Step 1]

The reaction of diethylamine of formula (XV) with carbonylsulfide gas of formula (XVI) at low temperature is followed by reaction of this solution with 1,2,4-oxadiazole of formula (XIII). 1,2,4-oxadiazole derivatives of the general formula (Ic) are obtained. Toluene is preferable as a solvent.

The reaction conditions are preferably warmed to 70 ℃ and stirred for 3 hours.

The method is represented by the following scheme.

In the above formula, R ¹ is as described above.

(Fourth method)

[Step 1]

0-acylamide oxime of general formula (XVII) was prepared by reacting ethylchloroformemate of general formula (VIII) with general formula (XVII), and then ring-closed to give 1,2,4- of formula (XIX). Obtain an oxadiazole derivative. At this time, the reaction conditions are the same as in the step 4-5 of the first method. It is preferable to use 2% aqueous sodium hydroxide solution in the ring-closure reaction.

[2 steps]

1,2,4-oxadiazole derivatives of formula (XIX) and phosphorous oxytrichloride of formula (XX) are reacted under an organic base catalyst to form l, 2,4-oxadiazole of formula (XXI). Obtain a derivative. As the organic base used at this time, pyridine and triethylamine are preferable.

The reaction temperature is preferably the boiling point temperature of the solvent.

[3 step]

1,2,4-oxadiazole derivatives of the general formula (XXI) and phenol of the general formula (XIV) are reacted in the presence of an inorganic base to obtain 1,2,4-oxadiazole derivatives of the general formula (Id). At this time, potassium inorganic acid is preferable as the inorganic base, and acetone is preferable as the solvent.

The reaction temperature is preferably the boiling point temperature of the solvent.

The method is represented by the following scheme.

Wherein R ¹ is as defined above and R represents phenyl with a substituent.

(5th method)

[Step 1]

0-acylamide oxime of general formula (XXIII) was prepared by reacting amide oxime of general formula (VIII) with ethyl oxalyl crolide of general formula (XXII), and then ring-opened to obtain 1, Obtain 2, 4-oxadiazole derivatives. At this time, the reaction conditions are the same as the conditions of step 4-5 of the first method. Preference is given to using pyridine or triethylamine in the ring closure reaction.

[2 steps]

Another 1, 2, 4-oxadiazole derivative of formula (Ie) is obtained by reacting a 1, 2, 4-oxadiazole derivative of formula (XXIV) with an amine of formula (XXV). As the solvent used at this time, anhydrous ethyl alcohol is preferable.

The reaction temperature is preferably 0 ° C.

The method is represented by the following scheme.

Wherein R ¹ is as defined above and R ² , R ³ represent hydrogen, alkyl, allyl, alkoxy and the like.

In the above 1-5 method, the nitrile, amide oxime, 0-acylamide oxime and final product 1,2,4-oxadiazole derivatives obtained by each step are distilled, crystallized and chromatized according to the physical properties of each compound. Isolation and purification were carried out according to methods commonly performed in the art, such as graphiography, and the identification of compounds was carried out using IR, NMR, mass spectrometry, and the like.

The present invention is explained in more detail by the following examples.

Example 1

(1) Synthesis of Ethyl Cyanoformate

트 336 2ml를 넣고 교반하면서 에틸클로로포름에이트 54.2g(0.5몰)을 서서히 적가하였다. 완전히 적가한후 2-3시간 가량 환류하여 생성된 염화나트륨을 여과하였다. 여액을 상압 증류하여 112-116℃에서 액체인 에틸시아노포름에이트 28.4g을 얻었다.(수율 58.6%)250 ml of methylene chloride, 24.5 g (0.5 mol) of sodium cyanide, 2.5 ml of water (1-2% of solvent) and ali

54 ml of ethyl chloroformate (0.5 mol) was slowly added dropwise with 2 ml of Tetra 336. After complete dropwise addition, the resulting sodium chloride was filtered by refluxing for 2-3 hours. The filtrate was atmospheric distilled to give 28.4 g of ethylcyanoformate as a liquid at 112-116 ° C. (Yield 58.6%)

NMR (CDCl ₃ , TMS) δ; 4.75-4.30 (q, 2H), 1.55-1.30 (t, 3H).

(2) Synthesis of Epithioxamate

25 g (0.25 mole) of ethyl cyanoformate was added to 70 ml of benzene, and the mixture was saturated by passing hydrogen sulfide gas while maintaining 0 ° C. 1 ml of triethylamine was added to this solution, and hydrogen sulfide gas was added again, and it reacted until the temperature which rose to 35 degreeC fell to 15-20 degreeC. It was left for 24 hours to obtain yellow needles. Recrystallization from benzene yielded 23 g of yellow crystals having a melting point of 65 DEG C. (yield 69.1%).

(3) Synthesis of ethoxycarbonylformamide oxime

6.95 g (0.1 mol) of hydroxylamine hydrochloride was added to 150 ml of ethyl alcohol in a solution of 2.3 g (0.1 mol) of sodium carbonate in 100 ml of ethyl alcohol. 13.3 g (0.1 mol) of ethylthiooxamate prepared in (2) was added to the filtered solution of sodium chloride, which was stirred for 1 hour and left for 24 hours. The solvent was concentrated under reduced pressure, and the resulting white crystals were washed with ether and dried under reduced pressure. 12.05 g of ethoxycarbonylformamide oxime was obtained as a white crystal having a melting point of 10 lC. (Yield 91.3%)

(4) Synthesis of 3-ethoxycarbonyl-5- (2 ', 4'-dichlorophenoxy) methyl-1,2,4-oxadiazole

After mixing 6.6 g (0.05 mole) of ethoxycarbonylformamide oxime and 11.9 g (0.05 mole) of 2,4-dichlorophenoxyacetyl chloride prepared in (3) with l50 ml of dioxane, trifluoroorborate Der 0.71 g (0.005 mol) was added and heated to reflux for 4 hours. The reaction solution was purified by column chromatography (eluent, benzene: ether = 1: 1) to give a colorless peak of 10.6 with a melting point of 94 ° C. (Yield 66.8%)

NMR (CDC1 _3, TMS) δ; 7.30-6.80 (m, 3H), 5.30 (s, 2H), 4.65-4.30 (q, 2H), 3.05 (s, 6H)

(5) Synthesis of 3-N, N-dimethylaminocarbonyl-5- (2 ', 4'-dichlorophenoxy) methyl-1,2,4-oxadiazole Synthesis in 50m1 of anhydrous ethyl alcohol in (4) 0.5 g (1.58 mol) of one compound was added thereto, and dimethylamine gas was injected with stirring at 0 ° C. The resulting solid was filtered to yield 0.4 g of a white solid having a melting point of 114-115 占 폚 (yield 80.3%).

Elemental Analysis (C12H11C1 ₂ N ₃ O ₃ )

Theoretic value: C; 45.59, H; 3.5l, N; 13.29.

Found: C; 45.64, H; 3.48, N; 13.32.

NMR (acetone d ₆ , TMS) δ; 7.60-7.30 (m, 3H), 5.65 (s, 2H), 3.05 (s, 6H)

Example 2-6

Prepared using the method of Example 1 from each substituted amine. Each compound was purified by column chromatography and the physical and elemental analysis values are shown in Table 1.

Example 7

(1) Synthesis of 3-hydrazido-5- (2 ', 4'-dichlorophenoxy) methyl-1,2,4-oxadiazole.

6.34 g (0.02 mol) of 3-ethoxycarbonyl-5- (2 ', 4'-dichlorophenoxy) methyl-1,2,4-oxadiazole synthesized in Example 4 (4) was ethyl alcohol. 3.4 ml of hydrazine hydrate was slowly added dropwise while maintaining the mixture at 150 ml while stirring at 15 ° C. The reaction solution was reacted at 0 ° C. for 30 minutes, and the resulting solid was filtered and washed with 10 ml of ethyl alcohol. The product was dried to give 4.2 g of white crystals having a melting point of 105 캜. (Yield 69.3%)

NMR (DMSO-d ₆ , TMS) δ; 7.45-7.10 (m, 3H), 6.30-5.90 (b, 3H), 5.50 (s, 2H)

(2) Synthesis of 3-azido-5- (2 ', 4'-dichlorophenoxy) methyl-1,2,4-oxadiazole.

3.33 g (0.11 mol) of 3-hydrazido-5-('2,4'-dicolophenoxy) methyl-1,2,4-oxadiazole was stirred by mixing 35 ml of concentrated hydrochloric acid and 14.5 ml of glacial acetic acid. . The reaction temperature was kept below 0 ° C. and a solution of 1.89 g of sodium nitrite dissolved in 5.3 ml of water was slowly added dropwise over 40 minutes. The reaction solution was left in dark for 2 hours, mixed with 100 ml of water and extracted with 50 ml of chloroform to obtain 2.43 g of white crystal lead product having a melting point of 103-104 ° C. from the organic layer. (Yield 70.4%)

NMR (CDC1 ₃ , TMS) δ; 7.45-7.15 (m, 3H), 5.25 (s, 2H)

(3) Synthesis of 3-methoxycarbonylamino-5- (2 ', 4'-dichlorophenoxy) methyl-1,2,4-oxadiazole.

Mix 1.5 g (0.0048 mol) of 3-azide-5- (2 ', 4'-dichlorophenoxy) methyl-1,2,4-oxadiazole and 0.32 g (0.01 mol) of methyl alcohol in 20 ml of dioxane After refluxing for 1 hour, the solvent was removed and the product obtained was recrystallized in a solvent (hexane: ethyl acetate = 2: l) to obtain 1.2 g of a white solid having a melting point of 90-91 ° C. (Yield 82.8%)

Elemental Analysis (C ₁₁ H ₉ Cl ₂ N ₃ O ₄ )

Theoretic value: C; 41.53, H; 2.85, N; 13.21

Found: C; 41.47, H; 2.90, N; 13.23

NMR (acetone d ₆ , TMS) δ; 7.70-7.60 (b, 1H), 7.60-7.20 (m, 3H), 5.65 (s, 2H), 4.01 (s, 3H)

Example 8

Synthesis of 3-N, N-diethylureido-5- (2 ', 4'-dichlorophenoxy) methyl-1,2,4-oxadiazole.

1.57 g (0.005 mol) of 3-azido-50 (2 ', 4'-dichlorophenoxy) methyl-1,2,4-oxadiazole was added to 20 ml of dried dioxane, and the mixture was heated and stirred under nitrogen at 100 ° C. The reaction was carried out for 30 minutes. 0.25 g (0.0055 mol) of dimethylamine was injected into the reaction solution, and the mixture was stirred overnight. The crystals formed in the reaction solution were filtered and washed with Ole and mixed with 100 ml of acetone and heated. After removing the insoluble substance, the solution was dried under reduced pressure to give 3-N, N-diethylureido-5- (2 ', 4'-dichlorophenoxy) methyl-1,2,4 as colorless crystals having a melting point of 93-94 占 폚. 0.9 g of oxadiazole was obtained (yield 55%).

Elemental Analysis (C ₁₂ H ₁₂ C1 ₂ NO ₃ )

Theoretic value: C; 43.54, H; 3.65, N; 16.92

Found: C; 43.55, H; 3.69, N; 16.90

NMR (DMSOd ₈ + acetone d ₆ , TMS) δ; 9.60 (b, 1H), 7.60-7.20 (m, 3H), 5.50 (s, 2H), 2.90 (s, 6H)

Example 9

(1) Synthesis of 2,4-dichlorophenoxyacetnitrile.

To 250 ml of acetone, 32.6 g (0.2 mol) of 2,4-dichlorophenol, 27.6 g (0.2 mol) of potassium carbonate, and 5.25 (0.2 mol) of chloroacenitrile were mixed and refluxed for 4 hours. After the solvent was removed, the product was extracted with ethyl acetate to obtain 34.5 g of a product. (Yield 85.3%)

(2) Synthesis of 2,4-dichlorophenoxyacetamide oxime.

Dissolve 14 g (0.2 mol) of hydroxylamine hydrochloride and 17 g (0.2 mol) of sodium bicarbonate in 70 ml of water, and then dissolve 34.5 g (0.17 mol) of 2,4-dichlorophenoxysetnitrile synthesized in (1) in 50 ml of ethyl alcohol. Added dropwise. After refluxing for 4-5 hours, the solvent was removed, and the concentrate was recrystallized from a solvent (hexane: ethyl acetate = 1: 1) to give 14.0 g of a white solid (yield 37.5%).

(3) Synthesis of 3- (2 ', 4'-dichlorophenoxy) methyl-5-ethoxycarbonyl-1,2,4-oxadiaol.

To 70 ml of chloroform, 4.69 g (0.02 mol) of 2,4-dichlorophenoxymethylamide oxime, 1.58 g (0.02 mol) of pyridine, and 2.72 g (0.02 mol) of ethyl oxalyl chloride were added and refluxed under stirring for 6 hours. After removing the solvent, the residue was purified by column chromatography (eluent, hexane: ethyl acetate = 2: 1) to obtain 4.9 g of a white solid at 73-74 ° C. (Yield 77.4%)

Elemental Analysis (C ₁₂ H ₁₀ C1 ₂ N ₂ O ₄ )

Theoretic value: C; 45.45, H; 3.18, N; 8.83

Found: C; 45.38, H; 3.22, N; 8.79

NMR (acetone d6, TMS) δ; 7.45-7.20 (m, 3H), 5.45 (s, 2H), 4.70-4.20 (q, 2H), 1.65-1.30 (t, 3H).

Example 10

Synthesis of 3- (2 ', 4'-dichlorophenoxy) methyl-5-amido-1,2,4-oxadiazole.

0.5 G (0.0016 mol) of 30 (2 ', 4'-dichlorophenoxy) methyl-5-ethoxycarbonyl-1,2,4-oxadiazole prepared in (3) of Example 9 was anhydrous ethyl alcohol. After dissolving in 50 ml, ammonia gas was injected while maintaining 0 ° C. After reacting for 30 minutes, the solvent was removed to obtain 43 g of white solid 0 having a melting point of 153-154 占 폚 (yield 98%).

Elemental Analysis (C ₁₀ H ₇ C1 ₂ N ₃ O ₃ )

Theoretic value: C; 41.69, H; 2.45, N; 14.59

Found: C; 41.75, H; 2.39, N; 14.53

NMR (DMSO-d ₆ , TMS) δ; 8.60-7.90 (b, 2H), 7.50-7.20 (m, 3H), 5.50 (s, 2H)

Example 11-12

Prepared using the method of Example 10 from each substituted amine. Each compound was purified by column chromatography and the physical and elemental analysis values are shown in Table 1.

Example 13

(1) Synthesis of O-ethoxycarbonyl (2 ', 4'-dichlorophenoxy) acetamide oxime.

11.75 g (0.05 mol) of 2,4-dichlorophenoxyacetamide oxime prepared in Example 9 (2), 5.43 g (0.05 mol) of ethylchloroformate and 5.06 g (0.05 mol) of triethylamine were 100 ml of methylene chloride. Mixed with and stirred for 1 hour. The reaction solution was washed with water, and the organic layer was dried over anhydrous sodium sulfate to remove the solvent, and then purified by column chromatography (eluent, benzene ethyl acetate = 1: 2) to give 14.6 g of colorless crystal having a melting point of 122 ° C. 95%)

NMR (CDC1 ₃ , TMS) δ; 7.25-7.01 (m, 3H), 6.30 (b, 2H), 4.50 (s, 2H), 4.40-4.01 (q, 2H), 1.50-1.15 (t, 3H)

(2) Synthesis of 3- (2 ', 4'-dichlorophenoxy) methyl-5-hydroxy-1,2,4-oxadiazole.

2.29 g (0.04 mol) of O-ethoxycarbonyl- (2 ', 4'-dichlorophenoxy) acetamide oxime was added to 100 ml of an aqueous 2% sodium hydroxide solution and refluxed for l hour. The reaction solution was cooled to room temperature, acidified to pH 1-2 with concentrated hydrochloric acid, and extracted with 250 g of ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, filtered off, and purified by column chromatography (eluent, chloroform: ethyl alcohol = 15: 1) to obtain 5.5 g of colorless crystals with a melting point of 134 ° C. (Yield 61%)

Elemental Analysis (C ₉ H ₆ C1 ₂ N ₂ O ₃ )

Theoretic value: C; 41.41, H; 2.32, N; 10.73

Found: C; 41.46, H; 2.35, N; 10.68

NMR (CDC1 ₃ , TMS) δ; 7.30-6.80 (m, 3H), 4.95 (s, 2H), 12.60 (b, 1H)

Example 14

Synthesis of 3- (2 ', 4'-dichlorophenoxy) methyl-5-chloro-1,2,4-oxadiazole.

5 g (0.019 mol) of 3- (2 ', 4'-dichlorophenoxy) methyl-5-hydroxy-1,2,4-oxadiazole prepared in (2) of Example 13, phosphorusoxytrichloride 19.7 g (0.12 mole) and pyridine 0.49 g (0.006 mole) were added and stirred to reflux for 10 hours. The reaction solution was cooled to room temperature, added to 200 ml of ice water, extracted with 150 ml of ether, the organic layer was dried over anhydrous magnesium sulfate, and the solvent was removed. The resulting residue was purified by column chromatography (eluent, benzene) to give a colorless color having a melting point of 56 ° C. 1.61 g of crystals were obtained. (Yield 29%)

Elemental Analysis (C ₉ H ₅ Cl ₃ N ₂ O ₂ )

Theoretic value: C; 38.67, H; 1.80, N; 10.02

Found: C; 38.71, H; 1.78, N; 10.09

NMR (CDC1 ₃ , TMS) δ; 7.50-7.01 (m, 3H), 5.20 (s, 2H)

Example 15

(1) Synthesis of ethyl- (4'-hydroxy) phenoxy-2-propionate.

33.03 g (0.3 mol) of hydroquinone, 55 g (0.3 mol) of ethyl 2-bromopropionate, and 41.46 g (0.3 mol) of potassium carbonate were added to 300 ml of acetone, and it heated and refluxed for 24 hours under stirring. The reaction solution was cooled to room temperature to remove the produced bromo potassium lead, and the residue obtained by liberation of the filtrate was extracted with 300 ml of ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was removed. The product obtained was purified by column chromatography (eluent, benzene, ether = 8: 2) to give 20.16 g of a highly viscous liquid (yield 32%).

NMR (CDC1 ₃ , TMS) δ; 6.70 (s, 4H), 6.01 (s, 1H), 4.40-4.01 (q, 2H), 1.40-1.l0 (t, 3H)

(2) 0.6 g (0.002 mol) of 3- (2 ', 4'-dichlorophenoxy) methyl-5-chloro-1,2,4-oxadiazole and ethyl- (4'-hydroxy) phenoxy- 0.45 g (0.002 mol) of 2-propionate and 0.28 g (0.002 mol) of potassium carbonate were added to 50 ml of acetone and heated to reflux for 3 hours.

The reaction solution was cooled to room temperature to remove the solvent, extracted with ethyl acetate, the organic layer was dried over anhydrous magnesium sulfate, and the solvent was removed. The product obtained was purified by column chromatography (eluent, benzene) to give 0.84 g of an oily substance. (93% yield).

Elemental Analysis (C ₂₀ H ₁₈ C1 ₂ N ₂ O ₆ )

Theoretic value: C; 53.00, H; 4.00, N; 6.18

Found: C; 53.04, H; 3.98, N; 6.13

NMR (CDC1 ₃ , TMS) δ; 7.30-6.80 (m, 7H), 5.01 (s, 2H), 4.90-4.50 (q, 1H), 4.40-4.10 (q, 2H), 180-1.60 (d, 3H), 1.40-1.10 (t, 3H )

Example 16

(2) of Example 15 with 3- (2'4'-chlorophenoxy) methyl-5-chloro-1,2,4-oxadiazole and α-nitro-4-colophenol obtained in Example 14 Get the same way. The compound was purified by column chromatography and the physical and elemental analysis values are shown in Table 1.

Example 17-18

3-benzyl-5-hydroxy-1,2,4-oxadiazole and 3- (4'-chlorophenyl) from phenylacetnitrile and 4-chlorobenzonitrile under the same conditions and methods as in Example 13 (2). ) -5-hydroxy-1,2,4-oxadiazole was synthesized, and 3-benzyl-5-chloro-1,2,4-oxadiazole and 3- ( 4'-chlorophenyl) -5-chloro-1,2,4-oxadiazolol was prepared. The products were reacted under the same conditions and methods as in Example 15 (2) to prepare a compound. Each compound was purified by column chromatography and the physical and elemental analysis values are shown in Table 1.

Example 19-21

In Example 14, the lead was 3- (2 ', 4'-dichlorophenoxy) ethyl-5-chloro-1,2,4-oxadiazole and 3-benzyl-5-chloro obtained in the same manner as in Example 14. The method of Example 15 (2) with phenol having a substituent of -1,2,4-oxadiazole and 3- (4'-chlorophenyl) -5-chloro-1,2,4-oxadiazole The reaction was carried out to prepare a compound. Each compound was purified by column chromatography and the physical and elemental analysis values are shown in Table 1.

Example 22

Synthesis of 3- (2 ', 4'-dichlorophenoxy) methyl-5-diethylphosphonyl-1,2,4-oxadiazole.

0.14 g (0.0005) mole of 3- (2 ', 4'-dichlorophenoxy) methyl-5-chloro-1,2,4-oxadiazole obtained in Example 14 in 0.2 ml of dried toluene and 0.2 g of driethylphosphate (0.00118 mol) was added and stirred to reflux for 12 hours. The reaction mixture was mixed with 50 ml of mole, extracted with 20 ml of ethyl acetate, dried over anhydrous magnesium sulfate, and the solvent was removed. The oily product was purified by column chromatography (eluent, benzene ether = 1: 1) to obtain a colorless liquid. 0.165 g of 3- (2 ', 4'-dichlorophenoxy) methyl-5-diethylphosphonyl-1,2,4-oxadiazole was obtained (yield 87%).

Elemental Analysis (C ₁₃ H ₁₅ C1 ₂ N ₂ O ₅ P)

Theoretic value: C; 40.90, H; 3.97, N; 7.35

Found: C; 40.95, H; 3.99, N; 7.40

NMR (CDC1 ₃ , TMS) δ; 7.30-6.90 (m, 3H), 5.20 (s, 2H), 4.50-4.01 (m, 4H), 1.50-1.10 (m, 6H)

Example 23

(1) Synthesis of n-propioamide oxime.

6.95 g (0.1 mol) of hydroxylamine hydrochloride and 5.3 g (0.05 mol) of sodium carbonate were dissolved in 50 ml of mole, and 5.5 g (0.1 mol) of n-propionitrile was dissolved in 50 ml of ethyl alcohol, mixed, and then smoked under stirring. It was refluxed for 6 hours. The reaction solution was concentrated, and the residue was extracted with 100 ml of ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was removed to obtain 4.93 g of n-propioamide oxime, a light blue viscous liquid (yield 55). %)

(2) Synthesis of O-chloroacetyl-n-propioamide oxime.

4.4 g (0.05 mol) of n-propioamide oxime prepared in (1) was added to 50 ml of dioxane and stirred. The reaction was carried out under the same conditions and methods as in (1), to obtain O-chloroacetyl-n-propioid oxime 7.lg. (Yield 86%)

(3) Synthesis of 3-ethyl-5-chloromethyl-1,2,4-oxadiazole.

4.1 lg (0.025 mol) of O-chloroacetyl-n-propioamide oxime prepared in (2) was added to 50 ml of dioxane and stirred. 0.3 g of boron fluoride ether was added to the reaction solution and heated to reflux for 6 hours. After completion of the reaction, the reaction solution was concentrated, and the residue was dried over 100 ml of ethyl acetate to remove the solvent. The product was purified by column chromatography (eluent, benzene: ether = 8: 2) to obtain 3.24 g of a colorless oil. (Yield 72%)

NMR (CDC1 ₃ , TMS) δ; 4.80 (s, 2H), 2.8-2.5 (q, 2H), 1.30-1.01 (t, 3H)

(4) Synthesis of 3-ethyl-5- [4 '-(1 "-ethoxycarbonyl-1" -methyl) methoxy] phenoxymethyl-1,2,4-oxadiazole

0.73 g (0.005 mol) of 3-ethyl-5-chloromethyl-1,2,4-oxadiazole prepared in (3) and ethyl- (4'-hydroxy) prepared in (1) of Example 15 1.05 g (0.005 mol) of phenoxy-2-propionate and 0.35 g (0.005 mol) of potassium carbonate were added to 50 ml of acetone and heated to reflux for 24 hours. The reaction solution was cooled to room temperature to remove the solvent, extracted with 50 ml of ethyl acetate and the organic layer was dried over anhydrous magnesium sulfate to remove the solvent. The residue was purified by column chromatography (eluent, benzene: ether = 8: 2) to obtain 1.3 g of an oil (yield 82%).

Elemental Analysis (C ₁₆ H ₂₀ N ₂ O ₅ )

Theoretic value: C; 59.99, H; 6.29, N; 8.74

Found: C; 60.04, H; 6.30, N; 8.70

NMR (CDC1 ₃ , TMS) δ; 6.80 (s, 4H), 5.05 (s, 2H), 4.80-4.40 (q-1H), 4.30-3.90 (q, 2H), 2.80-2.50 (m, 2H), 1.50-1.01 (m, 9H).

Example 24-26

5-Chloromethyl-1,2,4-oxadiazole prepared in the same manner as in Example 22 using 2-chloro-6-fluorobenzonitrile, phenylacetnitrile, and 2,4-dichlorophenoxysetnitrile The derivative was prepared in the same manner as in Example 22 (4) with ethyl- (4'-hydroxy) phenoxy-2-propionate prepared in Example (1). Each compound was purified by column chromatography, and the physical and elemental analysis are shown in Table 1.

Example 27

Synthesis of 3- (2 ', 4'-dichlorophenoxy) methyl-5- (N', N'-diethylcarbamoylthio) methyl-1,2,4-oxadiazole.

0.73 g (0.01 mol) of diethylamine was added to 50 ml of toluene, cooled to 0 ° C, and charged with 3 g (0.05 mol) of carbonyl silicide gas, followed by stirring for 30 minutes. 1.4 g (0.005 mol) of 3- (2 ', 4'-dichlorophenoxy) methyl-5-cloboromethyl-1,2,4-oxadiazole prepared in Example 26 was added to the reaction solution at 70 ° C. Warm and stir for 3 hours. The reaction solution was cooled to room temperature, washed with 50 ml of water, the organic layer was dried over anhydrous magnesium sulfate, and the solvent was removed. The resulting residue was purified by column chromatography (eluent, benzene: ether = 1: 1) to obtain 1.4 g. .

Elemental Analysis (C ₁₅ H ₁₇ C ₁₂ N ₃ O ₃ S)

Theoretic value: C; 46.16, H; 4.39, N; 10.77

Found: C; 46.11, H; 4.43, N; 10.80

NMR (CDC1 ₃ , TMS) δ; 7.30-6.80 (m, 3H), 5.20 (s, 2H), 4.30 (s, 2H), 3.60-3.20 (q, 4H), 1.30-1.01 (t, 6H)

Example 28-29

3-Benzal-5-chloromethyl-1,2,4-oxadiazole and 3- (2'-chloro-6'-fluoro) phenyl-5-chloro prepared in the same manner as in Example 22 (3) Methyl-1,2,4-oxadiazole was prepared in the same manner as in Example 27. Each compound was purified by column chromatography and the physical and elemental analysis values are shown in Table 1.

Example 30

(1) Synthesis of [4 '-(1 "-ethoxycarbonyl-1" -methyl) methoxy] phenoxyamide oxime.

3.2 g (0.015 mol) of ethyl- (4'-hydroxy) phenoxy-2-propionate prepared in Example 15 (1) and 2 g (0.02 mol) of cyanobromide were slowly reacted at 0 ° C. Stir well at 0 ° C. for 1 h. A solution of 1.04 g (0.015 mol) of hydroxy amine hydrochloride and 1.6 g (0.015 mol) of sodium carbonate dissolved in 20 ml of water was added to the reaction, followed by reaction at 30-40 ° C. for 3 hours. The reaction product was extracted with ethyl acetate and the solvent was removed to yield 3.01 g of a white solid. (Yield 75.3%)

(2) Synthesis of 3- [4 '-(1 "-ethoxycarbonyl-1" -methyl) methoxy] phenoxyamide oxime.

3.2 g (0.015 mol) of ethyl- (4'-hydroxy) phenoxy-2-propionate prepared in Example 15 (1) and 2 g (0.02 mol) of cyanobromide were slowly reacted at 0 ° C. Stir well at 0 ° C. for 1 h. A solution of 1.04 g (0.015 mol) of hydroxy amine hydrochloride and 1.6 g (0.015 mol) of sodium carbonate dissolved in 20 ml of water was added to the reaction, followed by reaction at 30-40 ° C. for 3 hours. The reaction was extracted with ethyl acetate, and then the solvent was removed to obtain 3.01 g of a white replacement. (Yield 75.3%)

(2) 3- [4 '-(1 "-ethoxycarbonyl-1" -methyl) methoxy] phenoxy-5- (2 ", 4-dichlorophenoxy) methyl-1,2,4-oxa Synthesis of azoles.

0.67 g (0.0025 mol) of [4 '-(ethoxycarbonyl-1 "-methyl) methoxy] phenoxyamide oxime prepared in (1) and 0.6 g of (2', 4'-dichlorophenoxy) acetyl chloride (0.0025 mol) was added to 50 ml of dioxane, followed by 0.2 ml of trifluoroboron ether, and refluxed for 6 hours.The solvent was removed, and the residue was purified by column chromatography (eluent, benzene: ether = 8: 2) to form a melting point. 0.7g of this yellow crystals which are 43 degreeC were obtained. (Yield 62%)

Elemental Analysis (C ₂₀ H ₁₈ C1 ₂ N ₂ O ₆ )

Theoretic value: C; 53.00, H; 4.00, N; 6.18

Stall: C; 53.05, H; 4.01, N; 6.14

R (CDCl ₃ , TMS) δ; 7.40-6.80 (m, 7H), 5.25 (s, 2H), 4.75 (q, 2H), 4.25 (q, 2H), 1.65 (d, 3H), 1.30 (t, 3H)

Example 31

Synthesis of 3- (N'.N'-diethylcarbamoylthio) methyl-5- (2 ', 4'-dichlorophenoxy) methyl-1,2,4-oxadiazole.

0.29 g (0.004 mole) of diethylamine was added to 50 ml of dried toluene, cooled to 0 ° C., 1.2 g (0.02 mole) of carbonylsulfide gas was added thereto, followed by stirring for 30 minutes. 0.6 g (0.002 mol) of 3-chloromethyl-5- (2 ', 4'-dichlorophenoxy) methyl-l, 2,4-oxadiazole prepared in Example 7 of Patent Application No. 1966 was added to the reaction solution. Warmed to 60 ° C. and stirred for 3 h. The reaction solution was cooled to room temperature, washed with 25 ml of mole, the organic layer was dried over anhydrous magnesium sulfate, and the solvent was removed. The resulting residue was purified by column chromatography (eluent, benzene: ether = 8: 2) to obtain 0.78 g. (50% yield)

Elemental Analysis (C ₁₅ H _l7 C1 ₂ N ₃ O ₃ S)

Theoretic value: C; 46.16, H; 4.39, N; 10.77

Found: C; 46.13, H; 4.40, N; 10.79

NMR (CDC1 ₃ , TMS) δ; 7.30-6.85 (m, 3H), 5.25 (s, 2H), 4.15 (s, 2H), 3.28 (q, 4H), 1.05 (t, 6H)

Herbicidal activity tests on the compounds of the present invention were carried out by the methods described below.

(Herbicidal activity test)

1. Herbicide activity test in field and dry condition

Sterilize the sandy loam mixed with an appropriate amount of fertilizer and place it in a test pot (field condition: 34cm ² , dry condition: 115cm ^* ). Seeds or underground seeds of tomato, soybean, corn, orchardgrass, amaranth, ragweed (or bergamot), silkworm, squirrel, silkworm, buckwheat, etc. Seeds are sown in pots under dry conditions, covered with finely ground soil and placed in a greenhouse. 4 kg / ha level test compound (field condition: 14 mg / pot, dry condition: 4 mg / pot) was dissolved in a solvent (acetone, ethanol, etc.) and then added to a nonionic surfactant (Tween-20) in water 1: Dilute to 1 and spray 14 ml per pot for field conditions and 4 ml per pot for dry conditions. At this time, the pretreatment soil treatment (pre) is treated on the 1st day after sowing, the post-germination foliage treatment (post) 8-8 days after sowing. After treatment with the drugs, they are grown in a greenhouse for 2-3 weeks and their herbicidal effects are examined by morphology and physiological observations. In other words, if the degree of herbicidal activity is evaluated as 0 for no control and 100 for complete control, the degree of herbicidal activity is recognized as having a herbicidal effect on the plant. Herbicide activity test results of the compounds in the field and dry conditions are shown in Table 2.

2. Paddy herbicide activity test under freshwater conditions

A small amount of fertilizer is placed on the bottom of a 60 cm ² (PRS, 1st) or 140 cm ² (2nd) round pot, and the sterilized sterilized soil is 5 cm deep. Seeds and perennial nutrients such as paddy fields, eggplants, mantis grass, mantis grass, knotweed flowers, needles, tadpoles, and turmeric on the surface of the soil are added to the surface of the seedlings (2-3 leaves). Plant each pot net 2cm deep. After transplanting, cut to 2cm depth and leave for 1 day, and then drip the prepared medicine as in field condition (4ml / pot for 4kg / ha level). At 2 weeks after drug treatment, herbicidal activity was examined according to the same survey criteria as field conditions. The herbicidal activity test results of the compounds under freshwater conditions are shown in Table 3.

The abbreviations of the plants used in the herbicidal activity test described above are shown in Table 4, and the herbicidal efficacy assay criteria are shown in Table 5.

Claims (9)

1,2,4-oxadiazole derivatives of the following formula (I).

Wherein R ¹ is dichlorophenoxymethyl, benzyl, ethyl, lower alkylamino carbonyl, amido, methoxycarbonyl amino, lower alkylureido, ethoxycarbonylalkoxy, diethylthiocarbamoylmethyl, halogen And one or two substituted allylaminocarbonyl, phenyl, and R ² is dichlorophenoxymethyl, hydroxy, chloro, diethylthiocarbamoylmethyl, ethoxycarbonylalkoxyalkoxymethyl, ethoxycarbon Carbonyl alkoxyphenoxy, dichlorophenoxy, nitrophenoxy, ethoxycarbonyl, amido, lower alkylaminocarbonyl, diethylphosphonyl. ^2. 1,2,4-oxadiazole derivatives according to claim 1, wherein R ¹ is lower alkylamino carbonyl and R ² is dichlorophenoxymethyl. A 1,2,4-oxydiazole derivative according to claim 1, wherein R ¹ is lower alkylureido and R ² is dichlorophenoxymethyl. ^2. 1,2,4-oxadiazole derivatives according to claim 1, wherein R ¹ is dichlorophenoxymethyl and R ² is lower alkylaminocarbonyl. The 1,2,4-oxadiazole derivative according to claim 1, wherein R ¹ is dichlorophenoxymethyl and R ² is ethoxycarbonylalkoxyalkoxyphenoxy. The 1,2,4-oxadiazole derivative according to claim 1 or 2, wherein the 1,2,4-oxadiazole derivative is 3-N, N-dimethylaminocarbonyl-5- (2 ', 4'-dicolophenoxy) -methyl -1,2,4-oxadiazole. The 1,2,4-oxadiazole derivatives according to claim 1 or 3, wherein the 1,2,4-oxadiazole derivative is 3-N, N-dimethylureido-5- (2'4'-dichlorophenoxy) methyl-1,2,4 A compound that is oxadiazole. The 1,2,4-oxadiazole derivative according to claim 1 or 4, wherein the 1,2,4-oxadiazole derivative is 3- (2 ', 4'-dichlorophenoxy) methyl-5-N, N-dimethylaminocarbonyl-1,2 , 4-oxadiazole. The 1,2,4-oxadiazole derivatives according to claim 1 or 5, wherein the 1,2,4-oxadiazole derivative is 3- (2 ', 4'-dichlorophenoxy) methyl-5- [4'-(1 "-ethoxycarbonyl -1 "-methyl) methoxy] phenoxy-1,2,4-oxadiazole.